Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine and DTPa-IPV-Hib when coadministered as a 3-dose primary vaccination schedule in The Netherlands: a randomized controlled trial.

BACKGROUND

Recent reviews have highlighted the unpredictability of immunologic interference when multivalent conjugated vaccines are coadministered with other pediatric vaccines.

OBJECTIVE

To evaluate immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix, GlaxoSmithKline Biologicals) and DTPa-IPV-Hib (Pediacel, Sanofi Pasteur MSD) when coadministered as a 3-dose primary vaccination course.

MATERIAL AND

METHODS

In a single-blind, single-center, randomized controlled trial in the Netherlands, healthy infants (n = 780) were randomly assigned (1:1:1) to receive either (1) PHiD-CV + DTPa-HBV-IPV/Hib (Infanrix Hexa, GlaxoSmithKline Biologicals), (2) PHiD-CV + DTPa-IPV-Hib, or (3) 7-valent pneumococcal conjugate vaccine (Prevenar/Prevnar, Pfizer Inc.) + DTPa-IPV-Hib at 2, 3, and 4 months of age. Blood samples were collected 1 month after dose 3. Diary cards were used to record safety and reactogenicity.

RESULTS

Antibody concentrations elicited by PHiD-CV coadministered with DTPa-IPV-Hib were noninferior to those following DTPa-HBV-IPV/Hib coadministration for 9 of 10 vaccines pneumococcal serotypes and protein D. For serotype 18C (conjugated to tetanus toxoid), the antibody concentration was higher with DTPa-HBV-IPV/Hib coadministration (1.73 vs. 1.07 μg/mL). The percentages of infants with antibody concentrations ≥0.2 μg/mL (68.9%-100% in the PHiD-CV + DTPa-HBV-IPV/Hib group vs. 64.9%-100% in the PHiD-CV + DTPa-IPV-Hib group) and with measurable opsonophagocytic activity (56.1%-100% in the PHiD-CV + DTPa-HBV-IPV/Hib group vs. 61.1%-100% in the PHiD-CV + DTPa-IPV-Hib group) were comparable for all serotypes in both PHiD-CV groups. Group differences in antibody responses to the DTPa-IPV-Hib antigens remained within the predefined limit for noninferiority. Safety and reactogenicity profiles were comparable across groups.

CONCLUSIONS

: PHiD-CV and DTPa-IPV-Hib were immunogenic and well tolerated when coadministered as a 3-dose primary vaccination course.